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Spatial transcriptomics reveals molecular mechanisms underlying neuroinflammatory and neurodegenerative sequelae of immune checkpoint inhibition [RNA-Seq]

GSE322681 Mus musculus (mouse) Spatial transcriptomics 20 samples Submitted 2026/06/09 Platform GPL34290
At a glance

Spatial transcriptomics · mouse · 20 samples

What it is
Spatial transcriptomicsGene activity measured with its position in a tissue section.
Organism
Mus musculus (mouse)
Samples
20 samples: 5 × hippocampus, CONTROL vs 5 × hippocampus, CONTROL + ICI vs 5 × hippocampus, MELANOMA vs 5 × hippocampus, MELANOMA + ICIGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Immune checkpoint inhibitors (ICIs) that block cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) signaling are among the most promising therapeutic approaches in tumor immunotherapy. We demonstrated that ICI disrupts synaptic integrity and neuronal plasticity by adversely altering microglial and neuro-immune homeostasis.
Read the full summary ↓
However, the cell type–specific molecular mechanisms underlying ICI-induced neuroinflammation and neuronal dysfunction remain poorly defined. To address this gap, we performed spatial transcriptomic profiling in a syngeneic melanoma mouse model using multiplexed error-robust fluorescence in situ hybridization (MERFISH) to map gene expression at single-cell resolution. By integrating spatial single-cell data with bulk RNA-seq from the hippocampus, we characterized the distribution of microglia, astrocytes, synaptic, and neuroinflammatory markers and determined how ICI reshapes hippocampal cellular composition in cancer-bearing and non-cancer mice brains. MERFISH revealed upregulation of microglial, astrocytic, oligodendrocytic and T cell markers post-ICI treatment, implicating pathways involved in neuroinflammation, synaptic function, and cellular signaling. Immunofluorescence analysis corroborated these findings in postmortem brains from patients treated with ICIs and demonstrated elevated microglial activation and astrogliosis, along with reduced expression of myelin sheath stability markers. Mechanistically, conditional T cell depletion in a transgenic mouse model revealed that ICI-mediated microglial activation is contingent on the presence of T cells, thus establishing a causal T cell-microglia crosstalk axis driving neuroinflammation. Collectively, this work provides a high-resolution framework for understanding ICI treatment-associated neurotoxicity and establishing a significant link with neuroinflammation-associated cognitive decline, while also revealing potential molecular targets for therapeutic intervention.
This dataset
Open GSE322681 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE322681_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Spatial studies usually ship Space Ranger style folders (count matrix plus tissue images). Look for them among the supplementary files.

Also filed as BioProject PRJNA1430961 and SRA study SRP680472. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 × hippocampus, CONTROL vs 5 × hippocampus, CONTROL + ICI vs 5 × hippocampus, MELANOMA vs 5 × hippocampus, MELANOMA + ICI

Supports a between-group comparison across 20 samples.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.